45 research outputs found
124I-HuCC49deltaCH2 for TAG-72 antigen-directed positron emission tomography (PET) imaging of LS174T colon adenocarcinoma tumor implants in xenograft mice: preliminary results
<p>Abstract</p> <p>Background</p> <p><sup>18</sup>F-fluorodeoxyglucose positron emission tomography (<sup>18</sup>F-FDG-PET) is widely used in diagnostic cancer imaging. However, the use of <sup>18</sup>F-FDG in PET-based imaging is limited by its specificity and sensitivity. In contrast, anti-TAG (tumor associated glycoprotein)-72 monoclonal antibodies are highly specific for binding to a variety of adenocarcinomas, including colorectal cancer. The aim of this preliminary study was to evaluate a complimentary determining region (CDR)-grafted humanized C<sub>H</sub>2-domain-deleted anti-TAG-72 monoclonal antibody (HuCC49deltaC<sub>H</sub>2), radiolabeled with iodine-124 (<sup>124</sup>I), as an antigen-directed and cancer-specific targeting agent for PET-based imaging.</p> <p>Methods</p> <p>HuCC49deltaC<sub>H</sub>2 was radiolabeled with <sup>124</sup>I. Subcutaneous tumor implants of LS174T colon adenocarcinoma cells, which express TAG-72 antigen, were grown on athymic Nu/Nu nude mice as the xenograft model. Intravascular (i.v.) and intraperitoneal (i.p.) administration of <sup>124</sup>I-HuCC49deltaC<sub>H</sub>2 was then evaluated in this xenograft mouse model at various time points from approximately 1 hour to 24 hours after injection using microPET imaging. This was compared to i.v. injection of <sup>18</sup>F-FDG in the same xenograft mouse model using microPET imaging at 50 minutes after injection.</p> <p>Results</p> <p>At approximately 1 hour after i.v. injection, <sup>124</sup>I-HuCC49deltaC<sub>H</sub>2 was distributed within the systemic circulation, while at approximately 1 hour after i.p. injection, <sup>124</sup>I-HuCC49deltaC<sub>H</sub>2 was distributed within the peritoneal cavity. At time points from 18 hours to 24 hours after i.v. and i.p. injection, <sup>124</sup>I-HuCC49deltaC<sub>H</sub>2 demonstrated a significantly increased level of specific localization to LS174T tumor implants (p = 0.001) when compared to the 1 hour images. In contrast, approximately 50 minutes after i.v. injection, <sup>18</sup>F-FDG failed to demonstrate any increased level of specific localization to a LS174T tumor implant, but showed the propensity toward more nonspecific uptake within the heart, Harderian glands of the bony orbits of the eyes, brown fat of the posterior neck, kidneys, and bladder.</p> <p>Conclusions</p> <p>On microPET imaging, <sup>124</sup>I-HuCC49deltaC<sub>H</sub>2 demonstrates an increased level of specific localization to tumor implants of LS174T colon adenocarcinoma cells in the xenograft mouse model on delayed imaging, while <sup>18</sup>F-FDG failed to demonstrate this. The antigen-directed and cancer-specific <sup>124</sup>I-radiolabled anti-TAG-72 monoclonal antibody conjugate, <sup>124</sup>I-HuCC49deltaC<sub>H</sub>2, holds future potential for use in human clinical trials for preoperative, intraoperative, and postoperative PET-based imaging strategies, including fused-modality PET-based imaging platforms.</p
Diagnostic usefulness of an amino acid tracer, α-[N-methyl-11C]-methylaminoisobutyric acid (11C-MeAIB), in the PET diagnosis of chest malignancies
On the perception of “segmental intonation”: F0 context effects on sibilant identification in German
Plasticity in neuromagnetic cortical responses suggests enhanced auditory object representation
Italian Association of Clinical Endocrinologists (AME) position statement: a stepwise clinical approach to the diagnosis of gastroenteropancreatic neuroendocrine neoplasms
The effect of basal vasodilation on hypercapnic and hypocapnic reactivity measured using magnetic resonance imaging
Cerebrovascular reactivity to vasodilatory hypercapnic and vasoconstrictive hypocapnic challenges is known to be altered in several hemodynamic disorders, which is often attributable to changes in smooth muscle-mediated vascular compliance. Recently, attenuated reactivity to hypercapnia but enhanced reactivity to hypocapnia was observed in patients with chronic stroke. We hypothesize that the latter observation could be explained by a change in the basal vascular tone. In particular, reduced cerebral perfusion pressure, as is prevalent in these patients, may cause vasodilation through autoregulatory mechanisms, and this compensatory baseline condition may alter reactivity to vasoconstrictive hypocapnic challenges. To test this hypothesis, a predilated vascular condition was created in young, healthy subjects (n=11; age=23 to 36 years) using inhalation of 4% CO2. Using blood oxygenation level-dependent functional magnetic resonance imaging at 3 T, breath holding and cued deep breathing respiratory challenges were administered to assess hypercapnia and hypocapnia reactivity, respectively. During the predilated condition, vasoconstrictive reactivity to hypocapnia was significantly (21.1%, P=0.016) enhanced throughout the gray matter, whereas there was no significant change (6.4%, P=0.459) in hypercapnic vasodilatory reactivity. This suggests that baseline vasodilation may explain the enhanced hypocapnia reactivity observed in some stroke patients, and that hypocapnia challenges may help identify the level of vascular compliance in patients with reduced cerebral perfusion pressure